Cancer is the second leading cause of mortality in the United States, with an estimated 1,444,180 new cases and 565,650 deaths in 2008. Cytotoxic agents, which are used in standard chemotherapy, non-specifically target all dividing cells resulting in dose-limiting toxicities. There is an urgent need to develop novel strategies that are more specifically targeted against the tumor.
The use of nanovectors holds the potential to revolutionize cancer chemotherapy by specifically targeting the tumor. A number of polymeric nanovectors are currently in development or in clinics, and are dramatically altering the pharmacodynamic and pharmacokinetic profile of the active agent. However, most of these polymeric constructs decrease the potency of the conjugated active agent, relying on increased uptake into the tumor for the improved therapeutic index.
Cisplatin is one of the mainstays in chemotherapy regimes for most types of Cancer (Kelland L. The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer. 2007 August; 7(8):573-84). However, its use is does-limited due to severe nephrotoxicity. Furthermore, the nanovector formulation of cisplatin, which is a first-line therapy for multiple cancers, has been a challenge.